text: Vesicle neurotransmitter antiporters are responsible for packaging neurotransmitters into vesicles in neurons. They utilize the electrochemical gradient of hydrogen protons across the membranes of synaptic vesicles to move neurotransmitters into them. This is essential for the process of synaptic transmission, which requires neurotransmitters to be released into the synapse to bind to receptors on the next neuron.
  One of the best characterized of these antiporters is the vesicular monoamine transporter (VMAT). It is responsible for the storage, sorting, and release of neurotransmitters, as well as for protecting them from autoxidation. VMAT's transport functions are dependent on the electrochemical gradient created by a vesicular hydrogen proton-ATPase. VMAT1 and VMAT2 are two isoforms that can transport monoamines such as serotonin, norepinephrine, and dopamine in a proton-dependent fashion. VMAT1 can be found in neuroendocrine cells, while VMAT2 can be found in the neurons of the central and peripheral nervous systems, as well as in adrenal chromaffin cells.
  Another important vesicle neurotransmitter antiporter is the vesicular glutamate transporter (VGLUT). This family of proteins includes three isoforms, VGLUT1, VGLUT2, and VGLUT3, that are responsible for packaging glutamate - the most abundant excitatory neurotransmitter in the brain - into synaptic vesicles. These antiporters vary by location. VGLUT1 is found in areas of the brain related to higher cognitive functions, such as the neocortex. VGLUT2 works to regulate basic physiological functions and is expressed in subcortical regions such as the brainstem and hypothalamus. Finally, VGLUT3 can be seen in neurons that also express other neurotransmitters.
  VMAT2 has been found to contribute to neurological conditions such as mood disorders and Parkinsons disease. Studies done on an animal model of clinical depression showed that functional alterations of VMAT2 were associated with depression. The nucleus accumbens, pars compacta of the substantia nigra, and ventral tegmental area - all subregions of the brain involved in clinical depression - were found to have lower VMAT2 levels. The likely cause for this is VMATs relationship with serotonin and norepinephrine, neurotransmitters that are related to depression. VMAT dysfunction may contribute to the altered levels of these neurotransmitters that occur in mood disorders.
  Lower expression of VMAT2 was found to correlate with a higher susceptibility to Parkinsons disease and the antiporters mRNA was found in all cell groups damaged by Parkinsons. This is likely because VMAT2 dysfunction can lead to a decrease in dopamine packaging into vesicles, accounting for the dopamine depletion that characterizes the disease. For this reason, the antiporter has been identified as a protective factor that could be targeted for the prevention of Parkinsons.
  Because alterations in glutamate release have been linked to the generation of seizures in epilepsy, alterations in the function of VGLUT may be implicated. A study was conducted where the VGLUT1 gene was inactivated in the astrocytes and neurons of an animal model. When the gene was inactivated in astrocytes, there was an 80% loss in the antiporter protein itself and, in turn, a reduction in glutamate uptake. The mice in this condition experienced seizures, lower body mass, and higher mortality rates. The researchers concluded that VGLUT1 function in astrocytes is therefore critical to epilepsy resistance and normal weight gain.
  There is a lot of evidence that the glutamate system plays a role in long-term cell growth and synaptic plasticity. Disturbances of these processes has been linked to the pathology of mood disorders. The link between the function of the glutamatergic neurotransmitter system and mood disorders sets up VGLUT as one of the targets for treatment.